This research program is concerned with exploring the genetic determinants of cellular and humoral immune responses. A coat colar mutation (lethal yellow, AY) in mice which is known to be associated with a high degree of tumor susceptibility also appears to be associated with a lower level of cellular immunity than control littermates. We are exploring the possibility that this reduced level of immune responsiveness may account for their high tumor susceptibility. We have demonstrated the existence of a gene in rats which determines the magnitude of the response of peripheral blood leukocytes to phytohemagglutinin and Concanavalin A. We have also shown that the susceptibility of rate to experimental allergic encephalomyelitis is determined by a gene closely linked to the major histocompatibility locus, Ag-B. We have shown that a single gene on the second chromosome of mice (lr-2 causes nonresponsiveness to the Ea-l erythrocyte alloantigens. We are exploring the possibility that lr-2 might cause tolerance to Ea-l at the T cell level, and are also attempting to determine whether the lr-2 and H-3 loci may be identical.